IP Library › Granted Patent US 12668624
Granted Patent B2
US 12668624 · App. 17/936,073 · Granted Jun 30, 2026

Antibody that binds to VEGF and PDGF-B

Inventors: Roland Beckmann (Singapore, SG); Kristian Hobolt Jensen (Vienna, AT); Hubert Kettenberger (Munich, DE); Janina Speck (Penzberg, DE)
Assignee: Hoffmann-La Roche Inc.
C07K16/22C07K2317/31C07K2317/55C07K2317/92
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Quick Facts
Patent No.
US 12668624
App. No.
17/936,073
Granted
Jun 30, 2026
Kind
B2
Abstract

The present invention relates to anti-VEGF/anti-PDGF-B antibodies and methods of using the same.

Claims (78)

1 . An antibody that binds to human VEGF and to human PDGF-B, comprising

a VH domain comprising

(a) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3,

(b) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 13, and

(c) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 14, and

a VL domain comprising

(d) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 15,

(e) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 16, and

(f) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 17; or

a VH domain comprising

(a) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3,

(b) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 29, and

(c) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 14, and

a VL domain comprising

(d) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 15,

(e) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 16, and

(f) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 17.

2 . The antibody of claim 1 , comprising L-FR-1 comprising the amino acid sequence of SEQ ID NO: 22; SEQ ID NO: 26; or SEQ ID NO: 32.

3 . The antibody of claim 1 , comprising

(a) a VH domain comprising an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 11; and (b) a VL domain comprising an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 21; or

(b) a VH domain comprising an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 11; and (b) a VL domain comprising an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 25; or

(c) a VH domain comprising an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 28; and (b) a VL domain comprising an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 25; or

(d) a VH domain comprising an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 28; and (b) a VL domain comprising an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 31.

4 . The antibody of claim 3 , comprising L-FR-1 comprising the amino acid sequence of SEQ ID NO: 22; SEQ ID NO: 26; or SEQ ID NO: 32.

5 . The antibody of claim 1 , comprising

a VH sequence of SEQ ID NO: 11 and a VL sequence of SEQ ID NO: 21;

a VH sequence of SEQ ID NO: 11 and a VL sequence of SEQ ID NO: 25;

a VH sequence of SEQ ID NO: 28 and a VL sequence of SEQ ID NO: 25; or

a VH sequence of SEQ ID NO: 28 and a VL sequence of SEQ ID NO: 31.

6 . The antibody of claim 1 , wherein the antibody is a Fab fragment.

7 . A pharmaceutical composition comprising the antibody of claim 1 and a pharmaceutically acceptable carrier.

8 . An antibody that specifically binds to human VEGF and to human PDGF-B, comprising

a VH sequence of SEQ ID NO: 11 and a VL sequence of SEQ ID NO: 12;

a VH sequence of SEQ ID NO: 11 and a VL sequence of SEQ ID NO: 21;

a VH sequence of SEQ ID NO: 11 and a VL sequence of SEQ ID NO: 25;

a VH sequence of SEQ ID NO: 28 and a VL sequence of SEQ ID NO: 25; or

a VH sequence of SEQ ID NO: 28 and a VL sequence of SEQ ID NO: 31.

9 . An antibody that binds to human VEGF and to human PDGF-B, comprising

a VH domain comprising

(a) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3,

(b) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 13,

(c) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 14, and

(d) a human heavy chain framework comprising

(i) FR1 comprising amino acid residues D1, L2, D25, G26, W27, and W28, and

(ii) FR3 comprising amino acid residues D73, D74, T75, N76, and R94; and

a VL domain comprising

(e) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 15,

(f) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 16,

(g) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 17, and

(h) a human light chain framework comprising

(i) FR1 comprising amino acid residue A1, I2, and

(ii) FR3 comprising amino acid residues H68, and E69; or

a VH domain comprising

(a) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 3,

(b) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 29,

(c) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 14, and

(d) a human heavy chain framework comprising

(i) FR1 comprising amino acid residues D1, L2, D25, G26, W27, and W28, and

(ii) FR3 comprising amino acid residues D73, D74, T75, N76, and R94; and

a VL domain comprising

(e) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 15,

(f) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 16,

(g) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 17, and

(h) a human light chain framework comprising

(i) FR1 comprising amino acid residue A1, I2, and

(ii) FR3 comprising amino acid residues H68, and E69;

wherein the numbering of the VH and VL domains is according to the Kabat numbering system.

10 . The antibody of claim 9 , comprising L-FR-1 comprising the amino acid sequence of SEQ ID NO: 22; SEQ ID NO: 26; or SEQ ID NO: 32.

11 . The antibody of claim 9 , comprising

(a) a VH domain comprising an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 11; and (b) a VL domain comprising an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 21; or

(b) a VH domain comprising an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 11; and (b) a VL domain comprising an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 25; or

(c) a VH domain comprising an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 28; and (b) a VL domain comprising an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 25; or

(d) a VH domain comprising an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 28; and (b) a VL domain comprising an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 31.

12 . The antibody of claim 11 , comprising L-FR-1 comprising the amino acid sequence of SEQ ID NO: 22; SEQ ID NO: 26; or SEQ ID NO: 32.

13 . The antibody of claim 9 , wherein an antibody Fab fragment of the antibody binds (i) to human VEGF121 with a KD of less than 50 pM as measured by surface plasmon resonance, and (ii) to human PDGF-B with a KD of less than 10 nM as measured by surface plasmon resonance.

14 . The antibody of claim 9 , wherein an antibody Fab fragment of the antibody exhibits an aggregation onset temperature of 68° C. or more.

15 . The antibody of claim 9 , wherein the antibody is a Fab fragment.

16 . A pharmaceutical composition comprising the antibody of claim 9 and a pharmaceutically acceptable carrier.